Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles.

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Kramer G, Schwarz S, Hagg M, Havelka AM, Linder S

Docetaxel induces apoptosis in hormone refractory prostate carcinomas during multiple treatment cycles.

Br J Cancer. 2006 Jun 5;94(11):1592-8.

PubMed ID

16685278 [ View in PubMed

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Abstract

Caspase-cleaved proteins are released from disintegrated apoptotic cells and can be detected in the circulation. We here addressed whether caspase-cleaved cytokeratin 18 (CK18-Asp396) can be used as a serum biomarker for assessment of the clinical efficiency of chemotherapy in hormone-refractory prostate cancer (HRPC). A total of 82 patients with HRPC were evaluated during 751 treatment cycles, either with estramustine (EMP)/vinorelbine or with EMP/docetaxel. The levels of CK18-Asp396 and of total CK18 were measured in patient serum before and during therapy by ELISA. Docetaxel induced significant increases in serum CK18-Asp396 (P<0.0001) and total CK18 (P<0.0002), suggesting induction of apoptosis. Similarly, vinorelbine induced increases in both CK18-Asp396 and CK18 (P<0.001 and 0.011). In contrast, EMP induced increases in total serum CK18 (P<0.0001), but not in CK18-Asp396 (P=0.13). The amplitudes of docetaxel-induced increases were associated with baseline prostate-specific antigen (PSA) and CK18 serum levels in these patients, consistent with tumoral origin of caspase-cleaved fragments. Docetaxel induced significant increases in CK18-Asp396 during second-, third- and fourth-line therapy and induced increased levels of CK18-Asp396 during treatment cycles 1-8. In contrast, vinorelbine induced significant increases only during cycles 1-3. In a subgroup of 32 patients that received EMP/vinorelbine in second line followed by EMP/docetaxel in third line, docetaxel induced stronger increases than vinorelbine (P=0.008). These results show that the CK18-Asp396 serum marker can be used to assess tumour apoptosis in vivo and suggest that the clinical efficiency of docetaxel in HRPC is due to induction of apoptosis during multiple treatment cycles.

DrugBank Data that Cites this Article

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Docetaxel	Approved Investigational	KRT18	3875	increased	docetaxel results in increased expression of KRT18 protein	12q13.13
Estramustine	Approved Investigational	KRT18	3875	increased	Estramustine results in increased expression of KRT18 protein	12q13.13
Vinorelbine	Approved Investigational	KRT18	3875	increased	vinorelbine results in increased expression of KRT18 protein	12q13.13